Our earlier basic studies have shown that MEG recordings during cognitive tasks have the ability to localize brain activity in comparable fashion to functional MRI. In specific, reduction in power in the beta frequency band at the cortex in general agrees with BOLD activation results. However, electrophysiological recordings such as the MEG/EEG have fine grained time dynamics not possible with other imaging techniques. We have also found that GABA (gamma-aminobutyric acid) concentration in the anterior cingulate cortex correlates with spatially localized resting MEG beta band power. We have expanded the cohort of well-matched subjects and isolated specific frequency band difference especially in the high gamma range (65 to 115 Hz). Differences in the degree of activation especially in frontal regions as indexed by beta desynchronization during a working memory task have been found between patients with schizophrenia compared to well siblings and healthy control volunteers. Previously we have seen that this activation reveals an interaction with genotype for the well-studied COMT marker. With groups of patients, siblings and controls matched for working memory task performance, patients show a distinct reduced DLPFC activation in apparent distinction to an increase in BOLD relative to task load. The MEG analysis isolates a working memory component that may reflect a different aspect of cortical processing. Recent analyses have been applied to a Sternberg memory task allowing the study of the relation of COMT to the components of memory. COMT differentially impacts MEG rhythms during the delay period compared to the recall (response). We have extended these results to examine differences in the high gamma band across groups. The relation of the different frequency bands to patterns of blood flow activation have revealed more specific targets for the neurophysiology underlying patient differences. We are now also comparing these differences in patients on and off anti-psychotic medication. It appears that medication may attenuate the PFC differences. Dani Rubenstein has completed his doctoral dissertation examining the comparison of MEG working memory activation to related fMRI and PET dopamine studies. We are also extending our genetic comparisons to examine modulation by SCN2A, a gene encoding the alpha-2 subunit of the sodium channel. Here we have now shown that the T genotype subgroup specifically shows greater high gamma band power during memory load compared to rest in middle frontal regions. This may be related to variation in cognitive performance across group, with MEG source localization showing significant differences in DLPFC and dACC for genotype by task interactions. This was presented in poster session at the Society For Biological Psychiatry annual meeting. As a follow on Carver and Fradkin have compared an auditory task MEG response that discriminate patients with schizophrenia from Healthy volunteers. This measure will be compared to neuropsychological and symptom scales to determine the biological subtype relationship. Several poster presentations have been accepted on this work. Differences in network patterns and dynamics are key to understanding underlying pathology in clinical groups. Previously Bassett et al. have shown that functional network variations in patient groups can be related to behavioral outcomes on cognitive activities. We have found distinct patterns of the temporal sequence of brain regions involved in these memory tasks that show a variety of individual differences across subjects. We are continuing to develop new measures to examine the flow of information in relation to cognitive task demand. We previously demonstrated that critical dynamics exist in resting MEG recordings. Comparison of patients with schizophrenia on similar measures suggest that their brains may operate at a different critical point that interacts with behavioral performance. New methods for uncovering the variety of network patterns have shown that cross-frequency coupling across brain regions may relate to both developmental and psychiatric trajectories.